The synapse or “gap” is the place where information is transmitted from one neuron to another. Synapses usually form between axon terminals and dendritic spines, but there are also axon-to-axon, dendrite-to-dendrite, and axon-to-cell body synapses. The neuron transmitting the signal is called the presynaptic neuron, while the neuron receiving the signal is called the postsynaptic neuron. Note that these designations are relative to a particular synapse; most neurons are both presynaptic and postsynaptic. There are two types of synapses, chemical and electrical, across which signals are transmitted.
For a signal to transmit across a chemical synapse, specific neurotransmitters are synthesized in the cell body, the axon, or the axon terminal. The neurotransmitter is stored in vesicles in the axon terminal until use.
When an action potential reaches the axon terminal, it depolarizes the membrane and opens voltage-gated Na+ channels. Na+ ions enter the cell, further depolarizing the presynaptic membrane. This depolarization causes voltage-gated Ca2+ channels to open. Calcium ions entering the cell initiate a signaling cascade that causes a release of small, membrane-bound vesicles, called synaptic vesicles, containing neurotransmitter molecules (Figure 1). These synaptic vesicles fuse with the presynaptic membrane.
Fusion of a vesicle with the presynaptic membrane causes neurotransmitters to be released into the synaptic cleft: the extracellular space between the presynaptic and postsynaptic membranes (Figure 2). The neurotransmitter diffuses across the synaptic cleft, binding to receptor proteins on the postsynaptic membrane.
The binding of a specific neurotransmitter causes particular ion channels, in this case ligand-gated channels, on the postsynaptic membrane to open. Neurotransmitters can either have excitatory or inhibitory effects on the postsynaptic membrane. For example, when acetylcholine is released at the synapse between a nerve and muscle (called the neuromuscular junction) by a presynaptic neuron, it causes postsynaptic Na+ channels to open. Na+ enters the postsynaptic cell, causing the postsynaptic membrane to depolarize. This depolarization, called an excitatory postsynaptic potential (EPSP), increases the probability that the postsynaptic neuron will fire an action potential. Release of neurotransmitter at inhibitory synapses causes inhibitory postsynaptic potentials (IPSPs), a hyperpolarization of the presynaptic membrane. For example, when the neurotransmitter GABA (gamma-aminobutyric acid) is released from a presynaptic neuron, it binds to and opens Cl- channels. Cl- ions enter the cell and hyperpolarize the membrane, reducing the probability that the neuron will fire an action potential.
Once neurotransmission has occurred, the neurotransmitter must be removed from the synaptic cleft to reset the postsynaptic membrane to receive another signal. This can be accomplished in three ways: the neurotransmitter can diffuse away from the synaptic cleft; it can be degraded by enzymes in the synaptic cleft; or it can be recycled (sometimes called re-uptake) by the presynaptic neuron. Several drugs act at this step of neurotransmission. For example, some drugs that are given to Alzheimer’s patients work by inhibiting acetylcholinesterase, the enzyme that degrades acetylcholine. This inhibition of the enzyme essentially increases neurotransmission at synapses that release acetylcholine. Once released, the acetylcholine stays in the cleft and can continually bind and unbind to postsynaptic receptors.
While electrical synapses are fewer in number than chemical synapses, they are found in all nervous systems where they play important and unique roles. The mode of neurotransmission in electrical synapses is quite different from that in chemical synapses. In an electrical synapse, the presynaptic and postsynaptic membranes are very close together and are actually physically connected by channel proteins forming gap junctions. Gap junctions allow current to pass directly from one cell to the next. In addition to the ions that carry this current, other molecules, such as ATP, can diffuse through the large gap junction pores.
There are key differences between chemical and electrical synapses. Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is unidirectional. Signaling in electrical synapses, in contrast, is virtually instantaneous (which is important for synapses involved in key reflexes), and some electrical synapses are bidirectional. Electrical synapses are also more reliable, as they are less likely to be blocked. They are also important for synchronizing the electrical activity of a group of neurons. For example, electrical synapses in the thalamus are thought to regulate slow-wave sleep. Disruption of these synapses can cause seizures.